Zobrazeno 1 - 10
of 46
pro vyhledávání: '"James J. S. Treanor"'
Autor:
Hannah Dou, Songli Wang, Hilary Plake Beck, Hantao Liu, Steven H. Olson, Toni Williamson, Philip Roveto, James J. S. Treanor, Frank Kayser, Guifen Xu, Ji Ma, Brian M. Fox, Qingwen Cheng, Lixia Jin
Publikováno v:
Journal of Medicinal Chemistry. 58:5256-5273
A high-throughput screen resulted in the discovery of benzoxazepine 1, an EP2 antagonist possessing low microsomal stability and potent CYP3A4 inhibition. Modular optimization of lead compound 1 resulted in the discovery of benzoxazepine 52, a molecu
Autor:
Essa Hu, Samer Chmait, Thomas T. Nguyen, Amy Porter, Kristin L. Andrews, Silke Miller, Carl Davis, Jennifer R. Allen, Robert M. Rzasa, James J. S. Treanor, Alexander J. Pickrell, Adrie D. Jones, Roxanne Kunz, Daniel B. Horne, Xiaoning Zhao, Matthew R. Kaller, Holger Monenschein, Ning Chen, Heather Eastwood, Jeffrey Clarine, Michael J. Frohn, Andreas Reichelt
Publikováno v:
Bioorganic & Medicinal Chemistry. 22:6570-6585
We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead comp
Autor:
Jianxia Shi, Xiaoning Zhao, Samer Chmait, Mary Dovlatyan, Silke Miller, Kristin L. Andrews, Geraldine Hill Della Puppa, James J. S. Treanor, Dianna Lester-Zeiner, Carl Davis, Essa Hu, Christopher Biorn, Jessica Able, Hang Chen, Jennifer R. Allen, Ji Ma
Publikováno v:
ACS Medicinal Chemistry Letters. 5:700-705
We report the discovery of novel imidazo[4,5-b]pyridines as potent and selective inhibitors of PDE10A. The investigation began with our recently disclosed ketobenzimidazole 1, which exhibited single digit nanomolar PDE10A activity but poor oral bioav
Autor:
Dah-Ren Hwang, John Castrillon, Shannon Rumfelt, Jennifer R. Allen, Essa Hu, Anissa Abi-Dargham, Carl Davis, Balu Easwaramoorthy, James J. S. Treanor, Hang Chen, Mark Slifstein
Publikováno v:
Nuclear Medicine and Biology. 41:343-349
Introduction Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the breakdown of cyclic nucleotides which are important secondary messengers in the central nervous system. Inhibition of PDE10A has been identified as a potential
Autor:
Dianna Lester-Zeiner, Christopher Biorn, Essa Hu, Jianxia Shi, James J. S. Treanor, Sharon Zhao, Jennifer R. Allen, Amy Porter, Kristin L. Andrews, Samer Chmait, Shannon Rumfelt, Aaron C. Siegmund, Roxanne Kunz, Ning Chen, Hang Chen, Carl Davis, Ji Ma
Publikováno v:
Journal of Medicinal Chemistry. 56:8781-8792
Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we d
Autor:
Samer Chmait, Adrie D. Jones, Amy Porter, Kristin L. Andrews, Xiaoning Zhao, Jennifer R. Allen, Shannon Rumfelt, Wenge Zhong, Essa Hu, James R. Falsey, Robert M. Rzasa, Steven W. Louie, James J. S. Treanor, Ning Chen
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 22:7371-7375
We report the discovery of a novel series of biaryl ethers as potent and selective PDE10A inhibitors. Structure-activity studies improved the potency and decreased Pgp-mediated efflux found in the initial compound 4. X-ray crystallographic studies re
Autor:
Randall W. Hungate, Jennifer R. Allen, Roxanne Kunz, James J. S. Treanor, Ji Ma, Carl Davis, Jianxia Shi, Essa Hu, Ning Chen, Dianna Lester-Zeiner, Dah-Ren Hwang, Hang Chen, Klaus Michelsen
Publikováno v:
ACS medicinal chemistry letters. 7(7)
We report the discovery of PDE10A PET tracer AMG 580 developed to support proof of concept studies with PDE10A inhibitors in the clinic. To find a tracer with higher binding potential (BPND) in NHP than our previously reported tracer 1, we implemente
Autor:
Dah-Ren Hwang, Geraldine Hill Della Puppa, Jamie Wong, Essa Hu, Thomas Nixey, Silke Miller, Hang Chen, Jessica Able, Dianna Lester-Zeiner, James J. S. Treanor, Robert Cho, Santosh Talreja, Roxanne Kunz, Jianxia Shi, Ji Ma, David C. Immke, Jennifer R. Allen, Christopher Biorn, Amy Porter, Klaus Michelsen, Shannon Rumfelt, Stephen Hitchcock
Publikováno v:
Journal of Medicinal Chemistry. 55:4776-4787
A radiolabeled tracer for imaging therapeutic targets in the brain is a valuable tool for lead optimization in CNS drug discovery and for dose selection in clinical development. We report the rapid identification of a novel phosphodiesterase 10A (PDE
Autor:
Jeffrey H. Kogan, Samer Chmait, Chun Li, Essa Hu, Michelle Lindstrom, Jiandong Zhang, Kristin L. Andrews, Roland Burli, Roxanne Kunz, Stephen Hitchcock, James J. S. Treanor, Ning Chen, Shannon Rumfelt
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 22:2262-2265
We report the discovery of 6,7-dimethoxy-4-(pyridin-3-yl)cinnolines as novel inhibitors of phosphodiesterase 10A (PDE10A). Systematic examination and analyses of structure–activity-relationships resulted in single digit nM potency against PDE10A. X
Autor:
Mqhele Ncube, Lillian Liao, Rami Tamir, Yunxin Bo, Narender R. Gavva, James J. S. Treanor, Partha P. Chakrabarti, Markian Stec, Nuria A. Tamayo, Mark H. Norman
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 18:5118-5122
Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintai